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Background: Pemphigus is a group of autoimmune blistering disorders that have been associated with dementia in previous studies. Mild cognitive impairment (MCI) can be the first stage of progression into dementia. The objective of the present study was to evaluate the frequency of MCI in pemphigus patients compared to a control group. Methods: This case‐control study included 80 patients with pemphigus referred to the dermatology clinics of Shohadaye Tajrish and Loghman Hakim hospitals, Tehran, Iran, in 2021. A group of 80 individuals without pemphigus who visited the same clinics for cosmetic consultation or interventions were regarded as controls. Age, sex, marital status, and education were recorded for all participants. Disease duration, medications, and severity were noted for pemphigus patients. The Persian version of the Montreal Cognitive Assessment (MoCA) test was used to assess cognitive function. Results: MCI was significantly more frequent in pemphigus patients than in controls (55% vs. 37.5%, P = 0.026). Furthermore, the total MoCA score was significantly lower in pemphigus patients compared to controls (23.98 ± 3.77 vs. 25.21 ± 3.45, P = 0.032); however, among MoCA's different domains, only the executive functions score was significantly lower in pemphigus patients (P = 0.010). After adjustment, multivariable logistic regression analysis revealed that every 1‐year higher education in patients decreased the odds of MCI by 52% (adjusted odds ratio = 0.483, 95% confidence interval 0.326; 0.715, P < 0.001). Conclusions: The frequency of MCI was found to be significantly higher, and overall scores of the MoCA test, as well as its executive function domain, were significantly lower among pemphigus patients in this study compared to the control group. Additionally, a higher level of education was associated with decreased odds of MCI in pemphigus patients. Identifying pemphigus patients with MCI through the use of the MoCA test can facilitate early intervention, enabling them to seek help and support. [ABSTRACT FROM AUTHOR]

Background and Purpose: Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G‐protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express. Experimental Approach: RNA sequencing and single cell qRT‐PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO). Candidate expression was evaluated in mice with UUO or diabetes or injected with adriamycin or folic acid. Intervention studies were conducted in mice with diabetes or UUO. Correlative histology was performed in human kidney tissue. Key Results: Transcription factor 21 (Tcf21)+ cells that expressed 2 or 3 of Postn, Acta2 and Pdgfra were highly enriched for fibrogenic genes and were defined as activated kidney fibroblasts. Tcf21+ α‐smooth muscle actin (α‐SMA)+ interstitial cells accumulated in kidneys of mice with UUO or diabetes or injected with adriamycin or folic acid, whereas renin‐angiotensin system blockade attenuated increases in Tcf21 in diabetic mice. Fifty‐six GPCRs were up‐regulated in single Tcf21+ kidney fibroblasts, the most up‐regulated being Adgra2 and S1pr3. Adenosine receptors, Adora2a/2b, were up‐regulated in Tcf21+ fibroblasts and the adenosine receptor antagonist, caffeine decreased Tcf21 upregulation and kidney fibrosis in UUO mice. TCF21, ADGRA2, S1PR3 and ADORA2A/2B were each detectable in α‐SMA+ interstitial cells in human kidney samples. Conclusion and Implications: Tcf21 is a marker of kidney fibroblasts that are enriched for fibrogenic genes in CKD. Further analysis of the GPCRs expressed by these cells may identify new targets for treating CKD. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc [ABSTRACT FROM AUTHOR]

Inotuzumab ozogamicin (InO) is an antibody‐drug conjugate approved for the treatment of relapsed/refractory B‐cell acute lymphoblastic leukemia (ALL). Several clinical trials are investigating InO in combination with low‐intensity chemotherapy or other anti‐ALL–targeted therapies in the salvage and frontline settings, notably in older adults who often cannot tolerate intensive chemotherapy and tend to have higher‐risk disease. InO is also increasingly used to bridge patients to hematopoietic stem cell transplantation (HSCT), in sequence with chimeric antigen receptor T‐cell therapy, to eliminate measurable residual disease and to prevent post‐HSCT relapse. Veno‐occlusive disease/sinusoidal obstruction syndrome is a potential complication of InO treatment, particularly when followed by HSCT. Herein, the authors review the historical development and current status of InO, strategies for mitigating the risk of InO‐related veno‐occlusive disease/sinusoidal obstruction syndrome, and future directions for InO research and clinical use. Inotuzumab ozogamicin is approved to treat relapsed/refractory B‐cell acute lymphoblastic leukemia but is increasingly used in other treatment settings. The authors review the historical development and current status of inotuzumab ozogamicin in adult B‐cell acute lymphoblastic leukemia. [ABSTRACT FROM AUTHOR]

Pharmacists play a key role in helping to identify and combat the spread of medical misinformation. To do this effectively, pharmacists need to be equipped with skills and tools to respond to medical misinformation as it relates to patient care. The lack of peer‐reviewed research on how to approach medical misinformation illustrates the need for specific strategies on how to identify, combat, and report medical misinformation. This article describes practical tactics pharmacists can use to teach learners the knowledge and skills necessary to reduce the spread of medical misinformation from various sources, including social media and artificial intelligence. [ABSTRACT FROM AUTHOR]

The chemical durability of perfluorosulfonic acid (PFSA) membranes is a topic of growing interest to meet Department of Energy (DOE) durability targets for heavy‐duty vehicle (HDV) applications. State‐of‐the‐art membranes like Nafion, rely on the use of cerium, heteropolyacids, and other inorganic additives to increase PFSA chemical durability. A less explored avenue for the oxidative stabilization of PFSA and hydrocarbon membranes is the use of organic antioxidants. No reversible organic antioxidant has been demonstrated to date which can enhance membrane lifetime by factors comparable to cerium. Here, ellagic acid (EA) is demonstrated as a promising radical scavenger for PFSA's. It is found that the incorporation of EA enhances the chemical durability of Nafion by 160%. EA, when incorporated with cerium as an electron donorenhances Nafion durability by at least 80% compared to a membrane incorporated with just cerium in DOE‐defined durability tests. EA is found to be reversible in acidic conditions like those of fuel cells and its reversibility could be further enhanced by the use of suitable co‐antioxidants. [ABSTRACT FROM AUTHOR]

In this paper, we model the revenue that could be raised from an annual and a one‐off wealth tax of the design recommended by Advani, Chamberlain and Summers in the Wealth Tax Commission's Final Report (2020). We examine the distributional effects of the tax, in terms of both wealth and other characteristics. We also estimate the share of taxpayers who would face liquidity constraints in meeting their tax liability. We find that an annual wealth tax charging 0.17 per cent on wealth above £500,000 could generate £10 billion in revenue, before administrative costs. Alternatively, a one‐off tax charging 4.8 per cent (effectively 0.95 per cent per year, paid over a five‐year period) on wealth above the same threshold, would generate £250 billion in revenue. To put our revenue estimates into context, we present revenue estimates and costings for some commonly proposed reforms to the existing set of taxes on capital. [ABSTRACT FROM AUTHOR]

The feasibility of measuring the surface potential decay of polystyrene (PS) film is investigated at room temperature by using Kelvin probe force microscopy (KPFM). The PS film was charged by an ion injection method utilizing Bruker's atomic force microscope (AFM) Nanoman module with a pulse duration of 1 ms, SCM‐PIT electrically conductive probe, and a voltage pulse of −250 mV. The surface potential decayed linearly on a semi‐log scale with time, where the time decay constant was quantified for relative humidity (RH) = 5% by KPFM at room temperature. The surface potential decayed due to the interaction of the PS film with the hydronium ions available in the environment. Furthermore, the effect of the material forms (film vs. microspheres) on the time decay constant at RH = 5% was investigated. The time decay constants measured using different methods exhibited excellent correlation with the AFM‐KPFM. This also confirmed that the results are independent of the material form (microspheres vs. film form). As a result, the proposed method can be used to measure the effect of RH for any PS surface (i.e., particles of various sizes and films) exposed to these environmental conditions. [ABSTRACT FROM AUTHOR]

Objectives: Tonsillectomy is the most common operation performed by otolaryngologists in the UK, despite this we have a poor understanding of the post‐operative recovery. We aimed to investigate post‐operative bleeding and pain following paediatric tonsillectomy using a patient diary. Design: Prospective observational cohort study. Setting: Multi‐centre study involving 12 secondary and tertiary otolaryngology units across the North of England. Patients were recruited from 1st March 2020 to 30th June 2022. Multilevel ordered logistic regression model statistics were performed. Participants: Children (≥4 years, ≤16 years) undergoing tonsillectomy (with or without adenoidectomy) for benign pathology. Main Outcome Measures: Frequency and severity of post‐operative bleeding.Intensity and pattern of post‐operative pain. Results: In total 297 children were recruited, with 91 (30.6%) diaries eligible for analysis. Post‐operative bleeding occurred in 44% of children. Most frequently blood in the saliva was reported (82.9%). Increasing age significantly increased bleeding odds by 17% per year (p =.001). Bleeding frequency decreased with higher surgeon grade (p =.003) and when performing intracapsular coblation tonsillectomy (p =.02) compared with other techniques. Lower age and intracapsular coblation tonsillectomy, against other techniques, significantly reduced rates of pain post‐operatively (p <.0001 and p =.0008). Conclusion: A high level of low‐level post‐operative bleeding was observed. Pain scores remained high for 5 days post‐operatively then gradually reduce to normal by day 13. Intracapsular coblation tonsillectomy appears to be superior to all other techniques in terms of reducing post‐operative bleeding and pain. These findings should be used to guide patients in the consent process to inform them of the expected nature of post‐surgical recovery. [ABSTRACT FROM AUTHOR]

Polybenzoxazine thermoset resins exhibit significant potential as precursors for carbon–carbon composites, owing to their high char yield upon pyrolysis. During pyrolysis, the resin is converted to an amorphous carbon‐rich material through a series of mechanisms, resulting in a linear increase of the glass transition temperature (TG) from 133 to 396°C at 0.48 pyrolytic conversion. To better understand this relationship, a non‐isothermal kinetic model was integrated, enabling the prediction of the TG onset, inflection, and endpoint based on the heat treatment protocol (process temperature (TP) vs. time) and the total volume of pyrolytic gases generated. By considering the TG behavior and anticipated gas effects, three distinct mechanisms were identified: (1) gas accumulation and matrix expansion leading to increased sample thickness (TG < TP), (2) crack network formation caused by gas‐pressure‐induced brittle failure (TG > TP), and (3) sample thickness reduction due to gas venting through the crack network (TG < TP). To validate this theory, thermal mechanical analysis was performed during pyrolysis, and changes in thickness (±ΔL/L0) were attributed to gas pressure‐related matrix deformation. Conversely, no change in ΔL/L0 indicated the formation of an interconnected crack network through which gases could vent without building a measurable internal pressure. [ABSTRACT FROM AUTHOR]

The transformation of abundantly available bioresources into specialty chemicals, particularly as consumer products, remains an important pursuit in chemical research. In this sense, the valorization of bio‐oil strategies that utilize stable and easy‐to‐handle chemical entity not only creates application‐oriented products but also helps in avoiding the usage of toxic and hazardous chemical sources. Recently, the valorization of α‐pinene (readily/naturally available terpenic compounds) has been explored to prepare a wide range of processes to access perfumery products and remains fast‐growing research for industrial and societal applications. Considering the valorization of α‐pinene, challenges for the synthetic and selective preparation of perfumery chemicals are centered around the design of the catalyst and the setting up of the precise reaction conditions. Extensive research is employed using diverse catalytic approaches to utilize α‐pinene to prepare important perfumery intermediates. In this review, the state‐of‐the‐art, recent advances and challenges in the utilization of α‐pinene are reviewed, emphasizing two main products, i.e., α‐campholenic aldehyde and carveol via α‐pinene oxide isomerization, and discussed the pertinent role of various homogeneous and heterogeneous catalytic systems. [ABSTRACT FROM AUTHOR]

In this study, we sought to determine the role of tRNA‐derived fragments in the regulation of gene expression during skeletal muscle cell proliferation and differentiation. We employed cell culture to examine the function of mt‐Ty 5' tiRNAs. Northern blotting, RT‐PCR as well as RNA‐Seq, were performed to determine the effects of mt‐Ty 5' tiRNA loss and gain on gene expression. Standard and transmission electron microscopy (TEM) were used to characterize cell and sub‐cellular structures. mt‐Ty 5'tiRNAs were found to be enriched in mouse skeletal muscle, showing increased levels in later developmental stages. Gapmer‐mediated inhibition of tiRNAs in skeletal muscle C2C12 myoblasts resulted in decreased cell proliferation and myogenic differentiation; consistent with this observation, RNA‐Seq, transcriptome analyses, and RT‐PCR revealed that skeletal muscle cell differentiation and cell proliferation pathways were also downregulated. Conversely, overexpression of mt‐Ty 5'tiRNAs in C2C12 cells led to a reversal of these transcriptional trends. These data reveal that mt‐Ty 5'tiRNAs are enriched in skeletal muscle and play an important role in myoblast proliferation and differentiation. Our study also highlights the potential for the development of tiRNAs as novel therapeutic targets for muscle‐related diseases. [ABSTRACT FROM AUTHOR]

Summary: There remains no one standard induction for nodal‐based peripheral T‐cell lymphoma (PTCL). We conducted a phase II study of lenalidomide plus CHOEP as a novel induction strategy. Patients received CHOEP at standard doses in combination with 10 mg of lenalidomide on days 1–10 of a 21‐day cycle for six cycles of therapy followed by observation, high‐dose therapy with autologous stem cell rescue, or maintenance lenalidomide per provider preference. Among 39 patients evaluable for efficacy, the objective response rate after six cycles was 69%, with complete response in 49%, partial response in 21%, stable disease in 0% and progressive disease in 13%. Thirty‐two patients (82%) completed full induction, and seven patients (18%) discontinued for toxicity, primarily hematologic. Any grade hematologic toxicity occurred in over 50% of patients, with grade 3 or 4 febrile neutropenia occurring in 35% of patients despite mandated growth factors. With a median followup of surviving patients of 21.3 months, the estimated 2‐year progression‐free and overall survival were 55% (95% CI 37%–70%) and 78% (95% CI 59%–89%), respectively. In sum, six cycles of lenalidomide plus CHOEP resulted in a modest response rate primarily due to hematologic toxicity, which prevented all patients from completing planned induction. [ABSTRACT FROM AUTHOR]

Silicoalumiophosphates (SAPOs) are microporous crystalline materials extensively utilized as adsorbents and catalysts. The present work utilized two strategies to synthesize nanocrystalline SAPO‐11. The first strategy involves a surfactant as a mesoporogen to reduce the crystallite size and increase the surface area for the materials synthesized at 200 °C in 2 days. In the second strategy, the synthesis temperature and time were significantly reduced to 160 °C and 3 h using propylene oxide as a pH accelerator. The reduction in the particle size and the improvement in the surface area were achieved using propyltriethoxysilane, which inhibited the growth of SAPO‐11 particles. The materials were thoroughly characterized using XRD, N2‐sorption, FTIR, pyridine‐adsorbed FTIR, electron microscopy, XPS, and NMR. The surfactant‐assisted synthesis formed a nanorod morphology with a large external and BET surface area. The low‐temperature synthesis involving silane as a growth inhibitor and propylene oxide as a pH modulator demonstrated a rectangular nanoplatelet morphology with a large surface area. The synthesis was scaled up to 10 g with no change in the experimental parameters. A synthesis strategy facilitating nuclei formation and retarding the growth of particle size will attract academia and industrial researchers to utilize these strategies for the manufacturing of zeolites of different frameworks on a large scale. [ABSTRACT FROM AUTHOR]

Patients with relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL), ineligible for or relapsing after autologous stem‐cell transplant or chimeric antigen‐receptor T‐cell therapies have poor outcomes. Several novel agents, polatuzumab vedotin, tafasitamab, loncastuximab tesirine, and selinexor, have been approved and offer new opportunities for this difficult to treat population. Studies are evaluating combination of these agents with chemotherapy and other emerging therapies. Additionally, advances in our understanding of DLBCL biology, genetics, and immune microenvironment have allowed for the identification of new therapeutic targets like Ikaros and Aiolos, IRAK4, MALT1, and CD47 with several agents in ongoing clinical trials. In this chapter we review updated data supporting the use of the approved agents and discuss other emerging novel therapies for patients with R/R DLBCL. [ABSTRACT FROM AUTHOR]

Aims: Subclassification of large B cell lymphoma (LBCL) is challenging due to the overlap in histopathological, immunophenotypical and genetic data. In particular, the criteria to separate diffuse large B cell lymphoma (DLBCL) and high‐grade B cell lymphoma (HGBL) are difficult to apply in practice. The Lunenburg Lymphoma Biomarker Consortium previously reported a cohort of over 5000 LBCL that included fluorescence in‐situ hybridisation (FISH) data. This cohort contained 209 cases with MYC rearrangement that were available for a validation study by a panel of eight expert haematopathologists of how various histopathological features are used. Methods and results: Digital whole slide images of haematoxylin and eosin‐stained sections allowed the pathologists to visually score cases independently as well as participate in virtual joint review conferences. Standardised consensus guidelines were formulated for scoring histopathological features and included overall architecture/growth pattern, presence or absence of a starry‐sky pattern, cell size, nuclear pleomorphism, nucleolar prominence and a range of cytological characteristics. Despite the use of consensus guidelines, the results show a high degree of discordance among the eight expert pathologists. Approximately 50% of the cases lacked a majority score, and this discordance spanned all six histopathological features. Moreover, none of the histological variables aided in prediction of MYC single versus double/triple‐hit or immunoglobulin‐partner FISH‐based designations or clinical outcome measures. Conclusions: Our findings indicate that there are no specific conventional morphological parameters that help to subclassify MYC‐rearranged LBCL or select cases for FISH analysis, and that incorporation of FISH data is essential for accurate classification and prognostication. [ABSTRACT FROM AUTHOR]

The OECD recently conducted a wide-ranging review of the wealth taxes already in operation within its member countries, and new empirical research has also examined the impacts of existing wealth taxes in a developing country context. Keywords: capital levy; tax policy; wealth tax EN capital levy tax policy wealth tax 389 395 7 10/27/21 20210901 NES 210901 MOTIVATION Around the world, proposals for new taxes on the I stock i of wealth (a "wealth tax") were gaining traction even before the fiscal tumult that has followed the COVID-19 pandemic. Additionally - of direct relevance to a wealth tax - it would useful to investigate whether these additional benefits (if any) scale directly with increasing wealth or whether they are only evident at extremely high levels of wealth. In the absence of a wealth tax from which to obtain administrative data on asset holdings, one option - as recommended by the Wealth Tax Commission in its final report - would be for official statistics agencies to incorporate a new booster sample for top wealth into their main household surveys on wealth. [Extracted from the article]

The bonding of a honeycomb core to the thermoset prepreg facesheets by co‐curing them allows one to manufacture composite sandwich structures in a single operation. However, the process is strongly dependent on the prescribed autoclave cure cycle. A previously developed physics‐based simulation can predict the bond quality as a function of the process parameters. The disadvantage of physics‐based simulations is the high computational effort needed to identify the optimal cure cycle to fabricate sandwich structures with desired bond‐line properties. Theory guided machine learning (TGML) methods have demonstrated their capabilities to reduce the computational effort for different applications. In this work, three TGML models are trained on a data set produced from physics‐based simulations to predict the co‐cure process of honeycomb sandwich structures. The accuracy of the TGML models were compared to select the best performing predictive tool. In addition to reduction of computational time by orders of magnitude, we demonstrate how the TGML tools can also quantify the contribution of each process parameter on the properties of the fabricated part. The most accurate model was implemented in an optimization routine to tune the input process parameters to obtain the desired properties such as the bond‐line porosity and facesheet consolidation level. This methodology could be extended to any process simulation of composites manufacturing processes. [ABSTRACT FROM AUTHOR]

Medical misinformation is more pervasive today because of widespread and near instantaneous dissemination of information via the internet and social media platforms. Consequences of medical misinformation may include decreased uptake of needed health care resources, delays in seeking care, vaccine hesitancy, medication non‐compliance, increased disease outbreaks and/or burden, and increased hospitalization and mortality. It disproportionately impacts underserved populations, including Black patients, those who identify as LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and more), and patients with reduced health literacy skills or who are digitally disadvantaged. Medical misinformation challenges health care professionals not only to provide the best care possible, but to assist patients in finding accurate information. Preprint publications, although potentially beneficial in rapidly disseminating new scientific discoveries, often have not undergone peer review and may contribute to the widespread propagation of inaccurate or overstated results, thereby perpetuating the spread of medical misinformation when it exists. The coronavirus disease 2019 (COVID‐19) pandemic highlighted the importance of practicing evidence‐based medicine and the need for cautious review of preprint publications and articles from predatory publishers in addition to usual and customary literature evaluation techniques. Everyone plays a role in preventing the spread of medical misinformation, with pharmacists uniquely positioned as trusted and highly accessible professionals who may help combat its spread. The goal of this article is to define medical misinformation and related terms, outline mechanisms by which it is spread, describe its clinical impact, highlight how it disproportionately impacts underserved populations, provide actionable strategies to prevent its spread, and give examples of practical tactics to help identify, correct, and alert individuals about the possible presence of medical misinformation. [ABSTRACT FROM AUTHOR]

Numerical modeling of flow through porous media and the simulation of liquid flow through orifices, channels and perforated walls, membranes, interlayers find applications in various fields. However, the mesh refinement needed to describe the detail at the scale of orifices within a domain multiple orders of magnitude larger raises numerical challenges. The present work proposes a pragmatic solution to model perforated layers partitioning a large porous media domain using 1D elements to model the holes and connect the 3D elements which represent the porous media. As an illustration, the approach is applied in liquid composite molding processes, and to the processing of large thick panels toughened with perforated interlayers. However, this work could be adopted in numerous fields. The combination of 3D and 1D elements to manage components with different dimensions has been used before, however no proper analysis of the loss of accuracy introduced has been conducted to our knowledge. A systematic parametric study is conducted to quantify the impact of the length of the domain, the number of interlayers, the diameter of the holes and the viscosity of the fluid on the loss of accuracy. Meshing rules and directions are provided to improve the accuracy of the simulations. [ABSTRACT FROM AUTHOR]

Objectives: Endovascular treatment (EVT) is the gold standard treatment for emergent large vessel occlusion (LVO). The benefit of EVT for emergent LVO in elderly patients (>80 years old) is still debated as they have been under‐represented in randomized controlled trials. Elderly patients with an emergent LVO are a growing population warranting further study. Materials & Methods: We included 225 consecutive patients treated with EVT for LVO either in the anterior or posterior circulation. The clinical outcome was assessed using the National Institute of Health Stroke Scale (NIHSS). Long‐term functional outcome was assessed using 90‐day modified ranking scale (mRS). Results: Neurological improvement: A five‐year higher age predicted a 0.43 higher mean NIHSS score after EVT (p =.027). After adjusting for confounders (influencing variables), the association between age and post‐interventional NIHSS was reduced and non‐significant (p =.17). At discharge, a five‐year higher age predicted a 0.74 higher mean NIHSS (p =.003). After adjusting for confounders this association was reduced and non‐significant (p =.06). Long‐term functional outcome: A five‐year higher age predicted a 0.20 higher mRS at three months (p <.001). When adjusting for confounders this number was reduced to 0.16, yet still highly significant (p <.001). Conclusions: Age seems to have a minor role in predicting neurological improvement after EVT but has an impact on long‐term functional outcome. The decision to perform or withhold EVT should therefore not solely be based on age. [ABSTRACT FROM AUTHOR]

Background: Solid organ transplant (SOT) recipients are challenging populations for antimicrobial stewardship interventions due to a variety of reasons, including immunosuppression, consequent risk of opportunistic and donor‐derived infections, high rates of infection with multi‐drug resistant organisms (MDROs), Clostridioides difficile, and need for prolonged antimicrobial prophylaxis. Despite this, data on stewardship interventions and metrics that address the distinct needs of these patients are limited. Methods: We performed a narrative review of the current state of antimicrobial stewardship in SOT recipients, existing interventions and metrics in this population, and considerations for implementation of transplant‐specific stewardship programs. Results: Antimicrobial stewardship metrics are evolving even in the general patient population. Data on metrics applicable to the SOT population are even more limited. Standard process, outcomes, and balancing metrics may not always apply to the SOT population. A successful stewardship program for SOT recipients requires reviewing existing data, applying general stewardship principles, and understanding the nuances of SOT patients. Conclusion: As antimicrobial stewardship interventions are being implemented in SOT recipients; new metrics are needed to assess their impact. In conclusion, SOT patients present a challenging but important opportunity for antimicrobial stewards. Abbreviations: SOT, antimicrobial stewardship program, MDRO, Clostridioides difficile infection, Centers for Disease Control and Prevention, Infectious Diseases Society of America, prospective audit and feedback, hematopoietic cell transplant, cytomegalovirus, trimethoprim‐sulfamethoxazole, surgical site infections, nucleic acid amplification testing, days of therapy, defined daily dose, and length of stay. [ABSTRACT FROM AUTHOR]

The production of biofuels, such as furfural ether and γ‐valerolactone (GVL) from biomass platform chemicals furfural (FFA) and Levulinic acid (LA) is of significant interest. In this study, a nanoporous inorganic‐organic Zr−phosphonate catalyst (ZrNPO3) was synthesized and employed in the selective production of GVL (98.2 %) via catalytic transfer hydrogenation of LA. The catalyst containing acid‐base sites was further used to produce biofuel molecules like GVL and furfuryl ether under a mild reaction condition via cascade furfural transformation. The GVL selectivity was further improved using phosphotungstic acid@ZrNPO3. The catalytic optimization studies were combined with poisoning studies and the detailed physicochemical characterization to acquire insight into the structure‐activity correlation and reaction mechanism. The synergistic presence of the Lewis acidity and basicity on the catalyst was responsible for its remarkable activity. Designing a single catalyst for the one‐pot tandem transformation of FFA to GVL would be highly motivating for catalysis researchers and industrialists. [ABSTRACT FROM AUTHOR]

For outcomes after auto-HCT, allogeneic transplant (allo-HCT), and chimeric antigen receptor T cell therapy (CAR-T), I TP53 i alteration must have been present at time of this therapy. Event free survival (EFS) after auto-HCT, allo-HCT, and CAR-T was defined as time from treatment to relapse, subsequent therapy, or death. OUTCOMES OF AUTOLOGOUS TRANSPLANT, ALLOGENEIC TRANSPLANT, AND CAR T CELL THERAPY IN TP53 ALTERED MANTLE CELL LYMPHOMA: A MULTI-INSTITUTION RETROSPECTIVE ANALYSIS. [Extracted from the article]

Background: Tissue engineering provides various strategies to fabricate an appropriate microenvironment to support the repair and regeneration of lost or damaged tissues. In this matter, several technologies have been implemented to construct close‐to‐native three‐dimensional structures at numerous physiological scales, which are essential to confer the functional characteristics of living tissues. Methods: In this article, we review a variety of microfabrication technologies that are currently utilized for several tissue engineering applications, such as soft lithography, microneedles, templated and self‐assembly of microstructures, microfluidics, fiber spinning, and bioprinting. Results: These technologies have considerably helped us to precisely manipulate cells or cellular constructs for the fabrication of biomimetic tissues and organs. Although currently available tissues still lack some crucial functionalities, including vascular networks, innervation, and lymphatic system, microfabrication strategies are being proposed to overcome these issues. Moreover, the microfabrication techniques that have progressed to the preclinical stage are also discussed. Conclusions: This article aims to highlight the advantages and drawbacks of each technique and areas of further research for a more comprehensive and evolving understanding of microfabrication techniques in terms of tissue engineering and regenerative medicine applications. [ABSTRACT FROM AUTHOR]

Diabetes mellitus was considered a fatal malady until the discovery, extraction and commercial availability of insulins. Numerous other classes of drugs ranging from sulfonylureas to sodium‐glucose co‐transporter‐2 inhibitors were then marketed. However, with the prevalence of diabetes mellitus increasing every year, many more drugs and therapies are under investigation. This review article aimed to summarize the significant developments in the pharmacotherapy of diabetes mellitus and outline the progress made by the recent advances, 100 years since insulins were first extracted successfully. Insulin analogues and insulin delivery pumps have further improved glycaemic control in diabetes mellitus. Cardiovascular and renal outcome trials have changed the landscape of diabetology, with some of these drugs also efficacious in nondiabetics. Newer drug delivery systems are being evaluated to improve the efficacy and reduce the dosing frequency and adverse effects of antidiabetics. Some newer drugs with novel mechanisms of action targeting type 1 and type 2 diabetes have also shown promise in recent clinical trials. These drugs include dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide 1‐agonists, glucokinase activators, anti‐CD3 monoclonal antibodies and glimins. Their efficacy needs to be evaluated in larger studies. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Objective outcome measures to monitor treatment response and guide treatment are lacking in chronic inflammatory demyelinating polyneuropathy (CIDP). In this study we aimed to evaluate the motor unit number index (MUNIX) as an outcome measurement in patients with CIDP and determine the correlation of MUNIX with functional and standard electrodiagnostic tests in a single follow‐up study. Methods: We evaluated MUNIX of the abductor pollicis brevis, abductor digiti minimi, and tibialis anterior (TA) muscles bilaterally. Muscle force was assessed by Medical Research Council Sum Score (MRCSS). Functional measures used were the Overall Neuropathy Limitation Score (ONLS) and the Rasch‐built Overall Disability Scale (R‐ODS) score at baseline and after 6 months of treatment. Standard electrophysiology was evaluated by the Nerve Conduction Study Score (NCSS). Results: Twenty patients were included at baseline, and 16 completed the follow‐up study. Significant correlations were found between the MUNIX sum score and both MRCSS and NCSS at baseline, between both the pinch strength and grip and upper limb MUNIX at baseline and follow‐up, and between MUNIX of TA and both lower limb MRCSSs with lower limb ONLS at baseline and follow‐up. Significant correlations also were found between MUNIX sum score change and MRCSS change, R‐ODS change, and ONLS change. Discussion MUNIX changes correlated with strength and electrophysiological improvements in CIDP patients. This suggests that MUNIX may represent a useful objective biomarker for patient follow‐up. [ABSTRACT FROM AUTHOR]

Chemicals, including some systemically administered xenobiotics and their biotransformations, can be detected noninvasively using skin swabs and untargeted metabolomics analysis. We sought to understand the principal drivers that determine whether a drug taken orally or systemically is likely to be observed on the epidermis by using a random forest classifier to predict which drugs would be detected on the skin. A variety of molecular descriptors describing calculated properties of drugs, such as measures of volume, electronegativity, bond energy, and electrotopology, were used to train the classifier. The mean area under the receiver operating characteristic curve was 0.71 for predicting drug detection on the epidermis, and the SHapley Additive exPlanations (SHAP) model interpretation technique was used to determine the most relevant molecular descriptors. Based on the analysis of 2561 US Food and Drug Administration (FDA)‐approved drugs, we predict that therapeutic drug classes, such as nervous system drugs, are more likely to be detected on the skin. Detecting drugs and other chemicals noninvasively on the skin using untargeted metabolomics could be a useful clinical advancement in therapeutic drug monitoring, adherence, and health status. [ABSTRACT FROM AUTHOR]

Keywords: Hodgkin lymphoma; first salvage therapy; autologous stem cell transplantation; brentuximab vedotin; bendamustine EN Hodgkin lymphoma first salvage therapy autologous stem cell transplantation brentuximab vedotin bendamustine e86 e90 5 04/30/20 20200501 NES 200501 We report the final 3-year efficacy and safety outcomes from a trial of outpatient administration of brentuximab vedotin (BV) plus bendamustine as a first salvage regimen in relapsed/refractory Hodgkin lymphoma (HL). Of 25 patients who underwent ASCT and six who did not continue BV monotherapy; 17 patients completed the maximum allowed 16 cycles of BV monotherapy. At the end of follow-up, 25 patients (83-3%) had no residual PN or Grade 1 PN, four patients had ongoing Grade 2 PN, and one patient had ongoing Grade 3 PN. [Extracted from the article]

Purpose: The US Preventive Services Task Force recommends lung cancer screening with Low‐Dose Computed Tomography (LDCT) in high‐risk individuals. Our objective was to identify demographic, health, and financial factors associated with screening uptake, with a focus on urban–rural differences. Methods: We analyzed data from the 2018 and 2019 Behavioral Risk Factor Surveillance System and its optional Lung Cancer Screening Module to examine factors associated with screening uptake among 20 states that administered the optional module. We compared differences in factors associated with uptake overall and by geographical regions and conducted multivariable logistic mixed‐effects regression, accounting for participant clustering by state to assess the impact of these factors on uptake. Findings: Overall 1,268 participants underwent LDCT screening with no significant differences observed between rural (16.3%) and urban residents (17.7%, p = 0.67). In multivariable models, rural residents did not differ significantly in their LDCT screening uptake (OR = 0.85; 95% CI: 0.67–1.09, p = 0.20), but uptake was significantly higher for participants with underlying chronic respiratory conditions, veterans, those with higher pack‐year history, and those with poor/fair general health and prior history of cancer. Uptake declined with age, higher education level, concerns about paying for medical care, and lack of primary care. Conclusions: Modifiable targets can be leveraged to increase LDCT screening. Based on significant predictors of screening uptake, clinicians should prioritize interventions that effectively consider smoking history as well as those identified as effective in veterans' health settings. Additionally, reducing structural barriers to care related to insurance and income will be key to reducing disparities. [ABSTRACT FROM AUTHOR]

Transverse myelitis has been reported as a complication of COVID‐19 in recent studies. Here, we report two cases of transverse myelitis related to COVID‐19. Both patients underwent plasma exchange after being treated with antibiotics and corticosteroids which lead to the recovery of one of them. [ABSTRACT FROM AUTHOR]

This article, published in Anaesthesia, discusses the surgical closure of the neck following thyroid surgery. The authors share their experiences with emergency management of thyroid hematomas and highlight the importance of understanding neck anatomy for anesthesiologists. They describe the key steps in wound closure, comparing skin closure with staples to glue. The authors suggest that guidelines should be updated to reflect the potential need to open the platysma and strap muscles in order to relieve pressure caused by post-thyroidectomy hematomas. [Extracted from the article]

Therapeutic drug monitoring (TDM) is the clinical practice of performing drug assays and interpreting results to maintain constant therapeutic concentrations in patients' bloodstream. Conventional TDM was started way back in the 1960s and served to optimise pharmacotherapy by maximising therapeutic efficacy by evaluating efficacy failure and monitoring drug compliance, while minimising adverse events, in drugs with a narrow therapeutic range. Currently, the scope of TDM has been extended to additional indications which are of importance to India. Apart from the conventional indications, TDM can also help combat drug resistance amongst patients treated with antimicrobials, including anti‐tubercular drugs and critically ill patients with compromised pharmacokinetics. TDM is also indicated for patients on antiretroviral drugs under specific clinical scenarios and is of high importance to India. Target concentration intervention (TCI) and apriori TDM (by merging TDM with pharmacogenomics) are emerging fields explored in developed nations. The authors sought to assess the evolution of TDM in India and evaluate the potential impact of newer indications in rationalising pharmacotherapy. In the mid‐1980s, TDM was presented to India. Despite showing some initial progress, its use is limited to conventional indications. Its utility is also challenged by cost and higher reliance on conventional prescribing practices. However, the newer indications such as antimicrobial resistance, tuberculosis and HIV, with their high prevalence in developing nations, present an opportunity for the growth of TDM in these countries. Indian clinician's awareness and buoyant demands alongside expert contributions from clinical pharmacologists could widen its scope. [ABSTRACT FROM AUTHOR]

Background: Heterogeneous evidence exists on the effect of coronavirus disease 2019 (COVID‐19) on the clinical outcomes of patients with cancer. Methods: A systematic review was performed using the Medline, Embase, and CENTRAL databases and the World Health Organization Novel Coronavirus website to identify studies that reported mortality and characteristics of patients with cancer who were diagnosed with COVID‐19. The primary study outcome was mortality, defined as all‐cause mortality or in‐hospital mortality within 30 days of initial COVID‐19 diagnosis. The pooled proportion of mortality was estimated using a random‐effects model, and study‐level moderators of heterogeneity were assessed through subgroup analysis and metaregression. Results: Among 2922 patients from 13 primarily inpatient studies of individuals with COVID‐19 and cancer, the pooled 30‐day mortality rate was 30% (95% CI, 25%‐35%). The overall pooled 30‐day mortality rate among 624 patients from 5 studies that included a mixture of inpatient and outpatient populations was 15% (95% CI, 9%‐22%). Among the hospitalized studies, the heterogeneity (I2 statistic) of the meta‐analysis remained high (I2, 82%). Cancer subtype (hematologic vs solid), older age, male sex, and recent active cancer therapy each partially explained the heterogeneity of mortality reporting. In multivariable metaregression, male sex, along with an interaction between the median patient age and recent active cancer therapy, explained most of the between‐study heterogeneity (R2, 96%). Conclusions: Pooled mortality estimates for hospitalized patients with cancer and COVID‐19 remain high at 30%, with significant heterogeneity across studies. Dedicated community‐based studies are needed in the future to help assess overall COVID‐19 mortality among the broader population of patients with cancer. In this meta‐analysis, the pooled 30‐day mortality rate is 30% (95% CI, 25%‐35%) among 2922 hospitalized patients diagnosed with both coronavirus disease 2019 and cancer. The interaction between median age and recent active cancer therapy, in addition to male sex, explains most of the between‐study heterogeneity. [ABSTRACT FROM AUTHOR]

Background: Tobacco consumption in smoking and non‐smoking forms has been consequential in the rise of oral cancer cases. Among different forms, epidemiological studies from Middle Eastern countries and rural parts of northern India have reported increasing association of oral cancer with waterpipe (hookah) smoking. However, molecular mechanisms and role played by waterpipe smoking in the onset of oral carcinogenesis remains unexplored. Methods: In this study, immortalized normal human oral keratinocytes were chronically treated with extracts of two varieties of waterpipe tobacco—crude tobacco and processed shisha. Phenotypic changes and molecular aberrations were examined using cell culture‐based assays and mass spectrometry‐based quantitative proteomic analysis, respectively. Bioinformatics analysis was utilized to analyze proteomics data and identify dysregulated pathways. Results: Our data indicate that chronic treatment with waterpipe tobacco extracts increased proliferation, invasion, migration, and significant dysregulation of protein expression in oral keratinocytes. Altered expression of proteins involved in interferon signaling pathway were observed with both varieties of tobacco. Overexpression of cholesterol metabolism and vesicle‐mediated transport proteins were identified exclusively in cells treated with crude tobacco extract. Bioinformatics analyses revealed different oncogenic response in oral cells based on the type of waterpipe tobacco used. Conclusions: This study may serve as a useful resource in understanding the early onset of oral cancer attributed to waterpipe smoking. [ABSTRACT FROM AUTHOR]

Herein, we report the catalytic activity of the copper and zinc doped ZrO2-based mixed metal oxide system towards the oxidation reaction. To study this attribute, different weight % loadings of copper and zinc supported on zirconia catalysts were synthesized by co-precipitation followed by the hydrothermal method. The synthesized catalysts were characterized by various physicochemical methods. X-ray analysis revealed that mainly cubic zirconia (111) planes were formed, and up to 0 to 25 wt.% Cu and Zn were doped in the zirconia lattice. Also, elemental mapping revealed uniform dispersion of Cu, Zn, Zr, and O elements. The catalytic activity of the synthesized zinc doped ZrO2-based mixed metal oxide system towards the oxidation reaction. To study this attribute, different weight % loadings of copper and zinc supported on zirconia catalysts were synthesized by co-precipitation followed by the hydrothermal method. The synthesized catalysts were characterized by various physicochemical methods. X-ray analysis revealed that mainly cubic zirconia (111) planes were formed, and up to 0 to 25 wt.% Cu and Zn were doped in the zirconia lattice. Also, elemental mapping revealed uniform dispersion of Cu, Zn, Zr, and O elements. The catalytic activity of the synthesized catalyst was studied for olefin epoxidation and alcohol oxidation reactions using aqueous tert-butyl hydrogen peroxide as an oxidant. Among all the synthesized catalysts, 2 wt.% doping of 1:1 Cu: Zn on ZrO2 gave almost complete olefin conversion with the best selectivity towards epoxides under optimized reaction conditions. Furthermore, the selected catalyst showed excellent substrate scope for different olefins and alcohol oxidation. Also, the catalyst was successfully recycled up to five cycles without affecting the conversion and selectivity. [ABSTRACT FROM AUTHOR]

Background: Patients with relapsed/refractory (R/R) Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) have a poor prognosis and limited treatment options. Methods: The efficacy of inotuzumab ozogamicin (InO), a humanized anti‐CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, was evaluated in R/R ALL patients in the phase 1/2 study 1010 (NCT01363297) and open‐label, randomized, phase 3 study 1022 (INO‐VATE; NCT01564784). This analysis focused specifically on Ph+ R/R ALL patients. In study 1022, Ph+ patients were randomly assigned 1:1 to InO (n = 22) or standard intensive chemotherapy (SC) (n = 27) and 16 Ph+ patients in study 1010 received InO. Results: In study 1022, rates of complete remission/complete remission with incomplete hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity (patients achieving CR/CRi) were higher with InO (CR/CRi = 73%; MRD = 81%) versus SC (CR/CRi = 56%; MRD = 33%). The corresponding rates in study 1010 were 56% (CR/CRi) and 100% (MRD). The hematopoietic stem cell transplantation (HSCT) rate in study 1022 was 41% versus 19% for InO versus SC; however, there was no benefit in overall survival (median OS: 8.7 vs 8.4 months; hazard ratio, 1.17 [95% CI, 0.64‐2.14]). The probability of being event‐free (progression‐free survival) at 12 months was greater with InO versus SC (20.1% vs 4.8%). Conclusion: Given the substantial improvement in responses and rates of HSCT, InO is an important treatment option for patients with R/R Ph+ ALL. Future studies need to consider better characterization of disease characteristics, more sensitive MRD measurements, MRD‐directed therapy before HSCT, and potentially combination therapies, including tyrosine kinase inhibitors. An analysis of 65 patients with relapsed/refractory Philadelphia chromosome‐positive acute lymphoblastic leukemia shows that patients receiving inotuzumab ozogamicin (InO) have higher rates of complete remission/complete remission with incomplete hematologic recovery, minimal residual disease negativity, and subsequent hematopoietic stem cell transplantation than those receiving standard intensive chemotherapy (SC). Although this does not result in prolonged progression‐free survival or overall survival compared with SC, InO remains an important treatment option for patients with resistant and difficult‐to–treat disease. [ABSTRACT FROM AUTHOR]

The influence of relative humidity on charge decay on polystyrene (PS) particles is investigated at room temperature by using Faraday cup and attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR) spectroscopy. The PS (2.8 ± 0.4 μm in diameter) particles were charged by using an ozone setup. The ozone charging source was from the free O‐ radicals generated from O3 dissociation on the surface of the PS particles resulting in carbonyl groups formation. The charge decayed exponentially, and the decay time constants were quantified using Faraday cup for various relative humidity conditions at room temperature. The charge decay due to the interaction of the PS particles with the environment was also investigated using ATR‐FTIR, where the CO stretching band at 1745 cm−1 was monitored. The decay of the CO on the PS particles is due to the reaction of the carbonyl groups with the hydronium ions [H3O]+. The reaction of CO with [H3O]+ is responsible for the time dependent charge decay. From both methods, the charge decay exhibited an exponential behavior, where the time decay constants measured from the two methods were in excellent correlation. The decay time constant increased linearly with increasing the RH. A generalized master charge decay curve is established for any PS surfaces (particles/films). [ABSTRACT FROM AUTHOR]

Antibiotics are among the leading causes of adverse drug events in older adults. Short‐course antibiotic therapy has been shown to work as well as the traditional longer durations for many types of infections. Antibiotic stewardship interventions including deprescribing strategies have shown a reduction in patient readmissions and mortality among older adults. We identified practice‐changing clinical trials focusing on three major domains of overprescribing antibiotics in older adults – community‐acquired pneumonia, urinary tract infections, and gram‐negative bacteremia. The selected articles underscore the safety and effectiveness of shorter durations of antibiotic treatment for infections in older adults, thus highlighting an opportunity for deprescribing in the aging population. By optimizing antibiotic use, we stand to reduce adverse events and enhance overall health outcomes in older adults. See other related Clin‐star papers by Mody et al. and Nair et al. in this issue. [ABSTRACT FROM AUTHOR]

Summary: Ibrutinib is associated with durable responses in patients with Waldenström macroglobulinaemia (WM). We hypothesized that response depth is predictive of progression‐free survival (PFS) in WM patients treated with ibrutinib. Using landmark analyses, we evaluated response depth in two cohorts of WM patients treated with ibrutinib monotherapy. The learning cohort was composed of 93 participants from two clinical trials, and the validation cohort of 190 consecutive patients treated off clinical trial. Rates of partial response (PR) or better at six months in learning and validation cohorts were 64% and 71% respectively (P = 0·29). In the learning cohort, three‐year PFS rates for patients who attained PR or better at six months versus not were 81% and 57% respectively (P = 0·009). In the validation cohort, three‐year PFS rates for patients who attained PR or better at six months versus not were 83% and 54% respectively (P = 0·008). In multivariate analyses, attaining PR or better at six months was associated with superior PFS in the learning [hazard ratio (HR) 0·38; P = 0·01] and validation cohorts (HR 0·18; P = 0·004). Attaining PR at six months on ibrutinib emerges as an intermediate outcome of interest and should be validated as surrogate for PFS in clinical trials evaluating Bruton tyrosine kinase inhibitors in WM. [ABSTRACT FROM AUTHOR]

The conventional approach to approximating the pharmacokinetics of drugs in patients with chronic kidney disease (CKD) only accounts for changes in the estimated glomerular filtration rate. However, CKD is a systemic and multifaceted disease that alters many body systems. Therefore, the objective of this exercise was to develop and evaluate a whole‐body mechanistic approach to predicting pharmacokinetics in patients with CKD. Physiologically based pharmacokinetic models were developed in PK‐Sim v8.0 (www.open-systems-pharmacology.org) to mechanistically represent the disposition of 7 compounds in healthy human adults. The 7 compounds selected were eliminated by glomerular filtration and active tubular secretion by the organic cation transport system to varying degrees. After a literature search, the healthy adult models were adapted to patients with CKD by numerically accounting for changes in glomerular filtration rate, kidney volume, renal perfusion, hematocrit, plasma protein concentrations, and gastrointestinal transit. Literature‐informed interindividual variability was applied to the physiological parameters to facilitate a population approach. Model performance in CKD was evaluated against pharmacokinetic data from 8 clinical trials in the literature. Overall, integration of the CKD parameterization enabled exposure predictions that were within 1.5‐fold error across all compounds and patients with varying stages of renal impairment. Notable improvement was observed over the conventional approach to scaling exposure, which failed in all but 1 scenario in patients with advanced CKD. Further research is required to qualify its use for first‐in‐CKD dose selection and clinical trial planning for a wider selection of renally eliminated compounds, including those subject to anion transport. [ABSTRACT FROM AUTHOR]

Summary: Patients with relapsed/refractory (R/R) non‐Hodgkin lymphoma (NHL) have limited options for salvage, and checkpoint blockade therapy (CBT) has little efficacy. Usage in solid malignancies suggests that CBT sensitises tumours to subsequent chemotherapy. We performed the first analysis of CBT on subsequent NHL treatment. Seventeen North American centres retrospectively queried records. The primary aim was to evaluate the overall response rate (ORR) to post‐CBT treatment. Secondary aims included progression‐free survival (PFS), duration of response (DOR) and overall survival (OS). Fifty‐nine patients (68% aggressive NHL, 69% advanced disease) were included. Patients received a median of three therapies before CBT. Fifty‐three (90%) discontinued CBT due to progression. Post‐CBT regimens included chemotherapy (49%), targeted therapy (30%), clinical trial (17%), transplant conditioning (2%) and chimeric antigen receptor T cell (CAR‐T) therapy (2%). The ORR to post‐CBT treatment was 51%, with median PFS of 6·1 months. In patients with at least stable disease (SD) to post‐CBT, the median DOR was significantly longer than to pre‐CBT (310 vs. 79 days, P = 0·005) suggesting sensitisation. Nineteen patients were transplanted after post‐CBT therapy. Median overall survival was not reached, nor affected by regimen. Prospective trials are warranted, as this may offer R/R NHL patients a novel therapeutic approach. [ABSTRACT FROM AUTHOR]

Background and objective: Optimal sample storage conditions are essential for non‐invasive prenatal testing of cell‐free fetal and total DNA. We investigated the effect of long‐term storage of plasma samples and extracted cfDNA using qPCR. Materials and methods: Fetal and total cfDNA yield and fetal fraction were calculated before and after storage of plasma for 0–6 years at −25°C. Dilution experiments were performed to investigate PCR inhibition. Extraction with or without proteinase K was used to examine protein dissociation. Storage of extracted cfDNA was investigated by testing aliquots immediately, and after 18 months and 3 years of storage at −25°C. Results: We observed a marked increase in the levels of amplifiable fetal and total DNA in plasma stored for 2‐3 years, and fetal fraction was slightly decreased after 3 years of storage. cfDNA detection was independent of proteinase K during DNA extraction in plasma samples stored >2 years, indicating a loss of proteins from DNA over time, which was likely to account for the observed increase in DNA yields. Measured fetal and total DNA quantities, as well as fetal fraction, increased in stored, extracted cfDNA. Conclusion: Fetal and total cell‐free DNA is readily detectable in plasma after long‐term storage at −25°C. However, substantial variation in measured DNA quantities and fetal fraction means caution may be required when using stored plasma and extracted cfDNA for test development or validation purposes. [ABSTRACT FROM AUTHOR]

Objectives: To investigate factors affecting the haemostatic success of non‐dissolvable intranasal packs in the management of acute epistaxis presenting to the emergency department (ED). Design: Prospective cohort study. Setting: A nationwide prospective audit examining epistaxis management at 113 sites in the UK over a 30‐day period. Participants: Patients 16 years or older, presenting to the ED with acute epistaxis managed with non‐dissolvable intranasal packs. Main outcome measures: The primary outcome was pack success, defined as successful haemostasis following nasal pack removal, not requiring further packing or surgical intervention or interventional radiology. Results: A cohort of 969 patients presented with epistaxis to the ED, with nasal packs being inserted in 54.4% by ED staff and by ENT in a further 18.9%. Overall, nasal packs were successful in 87.5%. Longer duration packs (≥21 hours) were more successful than shorter‐duration packs (89.9% vs. 84.3%, χ2P =.028). A patient survey supported longer packing duration. The most significant predictors of treatment failure were shorter packing duration (Odds Ratio (OR) = 2.3; 95% Confidence Interval (CI) = 1.4‐3.8), alongside ischaemic heart disease (OR = 1.9; 95% CI = 1.1‐3.3), normal admission haemoglobin (OR = 2.0; 95% CI = 1.2‐3.4) and no attempt at cautery following pack removal (OR = 2.5; 95% CI = 1.4‐4.2). Conclusions: The majority of epistaxis patients are packed by the ED prior to referral to ENT. Once inserted, nasal packs are highly successful, with data supporting the British Rhinological Society guidance of maintaining nasal packs for around 24 hours. Further work is needed to explore alternatives to non‐dissolvable intranasal packs to improve patient experience in epistaxis. [ABSTRACT FROM AUTHOR]

Purpose: Endovascular treatment (EVT) is traditionally performed by neurointerventional radiologists at tertiary medical centres imposing long transport ways to large vessel occlusion (LVO) stroke patients in rural areas. The purpose of this study is to evaluate the technical and clinical results over time at Stavanger University Hospital, a hospital without neurointerventional expertise, where trained general interventional radiologist performs EVT. Methods: All patients with LVO stroke treated with EVT from May 2009 to December 2018 were included in the analysis. Technical outcome was measured by the modified treatment in cerebral ischaemia (mTICI) score, functional outcome by the modified Rankin Scale (mRS), complications registered. Results: A total of 235 patients were treated with EVT. An angiographically good result (mTICI 2b or 3) could be seen in 66.7% of the patients treated the first year. In 2011, the year EVT with stent retrievers was introduced, the recanalization rate rose to 81.8%, and from 2014 onwards, it was stable around 80%. After introduction of aspiration together with stent retrievers in 2012, a good functional outcome (mRS 0‐2) was obtained in >40% of the treated patients. In 2018, 61.1% of the patients got a good functional outcome. Conclusions: Endovascular treatment of LVO stroke performed by general vascular interventional radiologist in close collaboration with diagnostic neuroradiologists and stroke neurologists can achieve technical revascularization results and clinical patient outcomes in line with international recommendations, and the randomized controlled studies performed. This approach may help to introduce EVT in geographical areas where this service is lacking due to the absence of neurointerventional specialists. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor (HER2) is an oncogene that codes for HER2 protein. The gene is amplified, and protein is overexpressed in 20% of patients and carries a poor prognosis. HER2‐positive tumors tend to be more aggressive and highly proliferative. In 2006, trastuzumab, a monoclonal antibody targeting HER2, was approved for use with chemotherapy as an adjuvant treatment for women with HER2‐positive breast cancer. The drug has shown improved survival rates for women with HER2‐positive breast cancer. As promised for survival in HER2‐positive patients continues with new research, and as novel drug approvals emerge, HER2 assessment plays a significant role in adjuvant and in metastatic setting. HER2 assays approved by the US Food and Drug administration include immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and bright field dual in situ hybridization (DISH). Accuracy of HER2 testing across laboratories has an impact on treatment as false‐negative testing can deprive the patients of trastuzumab therapy. The current review will focus on the variability of HER2 testing across laboratories and the potential impact on treatment. [ABSTRACT FROM AUTHOR]